title: Efficacy and safety of aclidinium bromide compared with placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease: results from a 6-week, randomized, controlled Phase IIIb study.
abstract: BACKGROUND
  This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks. The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6. Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.
  
  
  RESULTS
  Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]). Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (∆ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (∆ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6. Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo. Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05). Adverse-event (AE) incidence (28%) was similar between treatments. Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.
  
  
  CONCLUSIONS
  Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks. Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium. Aclidinium was generally well tolerated.
authors.affiliation: Insaf Respiratory Research Institute, Wiesbaden, Germany. j.beier@insaf-wi.de
authors.forename: Jutta
authors.initials: J
authors.lastname: Beier
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Kirsten
authors.forename: Robert
authors.initials: R
authors.lastname: Mróz
authors.forename: Rosa
authors.initials: R
authors.lastname: Segarra
authors.forename: Ferran
authors.initials: F
authors.lastname: Chuecos
authors.forename: Cynthia
authors.initials: C
authors.lastname: Caracta
authors.forename: Esther Garcia
authors.initials: EG
authors.lastname: Gil
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002940:Circadian Rhythm; D003371:Cough / Q000188:drug therapy / Q000209:etiology; D018450:Disease Progression; D004311:Double-Blind Method; D058995:Dry Powder Inhalers; D004417:Dyspnea / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005541:Forced Expiratory Volume; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D057240:Patient Preference; D010612:Pharyngitis / Q000139:chemically induced; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012135:Respiratory Sounds; D012602:Scopolamine Derivatives / Q000009:adverse effects / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D013997:Time Factors; D000069447:Tiotropium Bromide; D014326:Tropanes / Q000009:adverse effects / Q000627:therapeutic use*; D014987:Xerostomia / Q000139:chemically induced
chemical_list: D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D012602:Scopolamine Derivatives; D014326:Tropanes; C542859:aclidinium bromide; D000069447:Tiotropium Bromide